PROJECT SUMMARY The Zika virus (ZIKV) is a single-stranded RNA virus that is mainly transmitted to humans through infected Aedes mosquitos. The ZIKV disease is evident in approximately 20% of infected people. There is growing evidence suggesting the deleterious effects of ZIKV on pregnant women and their infants. In fact, the World Health Organization previously declared ZIKV a public health emergency, yet we still do not understand how this disease impacts early clinical outcomes necessary for an infant to thrive and develop, like sucking and feeding. Sucking and feeding behaviors are extremely important clinical markers, as these behaviors require a tremendous amount of integration across multiple systems (neural/cardio/respiratory), including more than five cranial nerves, and coordination among 26 muscle pairs (8, 9). In fact, sucking and feeding abnormalities in early infancy have been viewed as potential markers of neonatal brain injury (17,18,19). There remains a significant gap in knowledge as to how exposure to ZIKV in utero influences sucking, feeding and cardiorespiratory patterning in infants. Therefore, this project aims to quantitatively examine how non-nutritive sucking (NNS; AIM 1), oral feeding (AIM 2), and cardiorespiratory patterning (heart-rate, respiratory rate, heart- rate variability; AIM 3) develop in the following groups of infants (n=200) born in Puerto-Rico: control infants who were not exposed to ZIKV during pregnancy (Group 1), infants who were exposed to ZIKV during pregnancy without evidence of congenital ZIKV syndrome (CZS; defined by the following: severe microcephaly, brain anomalies, ocular findings, congenital contractures, and neurological impairments (10)) (Group 2), and infants who were exposed to ZIKV during pregnancy with evidence of CZS (Group 3). Our hypothesis is that infants exposed to ZIKV during pregnancy with evidence of CZV (Group 3) will perform worse on their NNS, oral feeding and cardiorespiratory outcomes compared to infants in Groups 1 and 2?with infants in Group 2 performing worse than the control infants (Group 1). We will leverage the ongoing ZIKV project in Puerto Rico, entitled ?Zika in Infants and Pregnancy (ZIP)?, already underway, to recruit infants from their cohort over the two-year study (see letter of support). Several features of this study provide an unprecedented level of power for identifying the connection between ZIKV exposure and early sucking, feeding and cardiorespiratory behaviors, including quantitative assessments of these measures sampled soon after birth with comparisons across three infant groups. Findings from this work could have broad implications for advancing our knowledge of ZIKV, and an immediate impact on clinical therapies. More specifically, the proposed studies are likely to (1) provide essential data on how ZIKV exposure influences sucking, feeding, and cardiorespiratory development; (2) examine the utility of using these behaviors as an early biomarker of development in infants exposed to ZIKV, and (3) shift how researchers and clinicians assess and treat these behaviors with the goal of improving these outcomes allowing these infants to grow, develop, and thrive.